‘Rejuvenation’ protects neurons in mouse models of Parkinson’s disease

@article{Chan2007RejuvenationPN,
  title={‘Rejuvenation’ protects neurons in mouse models of Parkinson’s disease},
  author={C. Savio Chan and Jaime N. Guzman and Ema Iliji{\'c} and Jeff N. Mercer and Caroline Rick and Tatiana Tkatch and Gloria E. Meredith and Dalton James Surmeier},
  journal={Nature},
  year={2007},
  volume={447},
  pages={1081-1086}
}
Why dopamine-containing neurons of the brain’s substantia nigra pars compacta die in Parkinson’s disease has been an enduring mystery. Our studies suggest that the unusual reliance of these neurons on L-type Cav1.3 Ca2+ channels to drive their maintained, rhythmic pacemaking renders them vulnerable to stressors thought to contribute to disease progression. The reliance on these channels increases with age, as juvenile dopamine-containing neurons in the substantia nigra pars compacta use… 

Figures from this paper

Could rejuvenating neurons protect against Parkinson's?
TLDR
The team found that isradipine reduced the loss of SNc neurons and prevented the development of motor deficits in a mouse model of PD and found that dihydropyridines reduce the incidence of PD.
Neurodegenerative diseases: Channel switch rejuvenates neurons
TLDR
Adult SNc dopaminergic neurons could be rejuvenated in vivo using isradipine, and the potential of this approach to ameliorate PD in humans could soon be evaluated in clinical trials.
A molecular basis for the increased vulnerability of substantia nigra dopamine neurons in aging and Parkinson's disease
TLDR
Systemic administration of isradipine, a dihydropyridine blocker of these channels, forces dopaminergic neurons in rodents to revert to a juvenile, L‐type Ca2+ channel independent mechanism to generate autonomous activity, suggesting protection against toxins that produce experimental Parkinsonism.
What causes the death of dopaminergic neurons in Parkinson's disease?
HCN Channelopathy in External Globus Pallidus Neurons in Models of Parkinson’s Disease
TLDR
It is concluded that the loss of pacemaking was a consequence, rather than a cause, of key network pathophysiology, a conclusion that is consistent with the ability of L-type channel antagonists to attenuate silencing after DA depletion.
Parkinson's Disease: Return of an Old Prime Suspect
...
1
2
3
4
5
...

References

SHOWING 1-10 OF 88 REFERENCES
Behavioral models of Parkinson's disease in rodents: A new look at an old problem
  • G. Meredith, U. Kang
  • Biology, Psychology
    Movement disorders : official journal of the Movement Disorder Society
  • 2006
TLDR
How investigations in rodents of skilled forepaw actions, including placing, grooming, or foot faults, have clear correlates in Parkinson's disease, and are, therefore, the most sensitive ways of detecting motor impairment following dopamine loss from the basal ganglia of rodents are explained.
Stages in the development of Parkinson’s disease-related pathology
TLDR
The synucleinopathy, idiopathic Parkinson's disease, is a multisystem disorder that involves only a few predisposed nerve cell types in specific regions of the human nervous system that manifests itself in all of its clinical dimensions.
Molecular Pathways of Neurodegeneration in Parkinson's Disease
TLDR
Strategies aimed at restoring complex I activity, reducing oxidative stress and α-synuclein aggregation, and enhancing protein degradation may hold particular promise as powerful neuroprotective agents in the treatment of PD.
Excitotoxicity and nitric oxide in Parkinson's disease pathogenesis.
  • M. Beal
  • Biology, Chemistry
    Annals of neurology
  • 1998
TLDR
The results raise the prospect that excitatory amino acid antagonists for neuronal NO synthase inhibitors might be useful in the treatment of PD.
Uneven pattern of dopamine loss in the striatum of patients with idiopathic Parkinson's disease. Pathophysiologic and clinical implications.
TLDR
It is proposed that the motor deficits that are a constant and characteristic feature of idiopathic Parkinson's disease are for the most part a consequence of dopamine loss in the putamen, and that the dopamine-related caudate deficits are less marked or restricted to discrete functions only.
Parkinson's--Divergent Causes, Convergent Mechanisms
TLDR
The different possible causes of PD are discussed in light of new work identifying mutations in the putative mitochondrial protein kinase PINK1 as a cause of familial PD.
...
1
2
3
4
5
...